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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
人脐带血间充质干细胞来源外泌体作为多西他赛与 miR-125a 的高效纳米载体：处方优化与抗转移行为
英文原题：Human umbilical cord blood-mesenchymal stem cell derived exosomes as an efficient nanocarrier for Docetaxel and miR-125a: Formulation optimization and anti-metastatic behaviour.
查看英文原题
Human umbilical cord blood-mesenchymal stem cell derived exosomes as an efficient nanocarrier for Docetaxel and miR-125a: Formulation optimization and anti-metastatic behaviour.
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中文摘要
目的
外泌体作为纳米载体共同递送生物制剂和小分子抗癌药仍处于早期阶段。本研究考察人脐带血间充质干细胞（hUCBMSC）来源外泌体，能否共同递送抑癌miR-125a和微管去稳定剂多西他赛（DTX），抑制小鼠三阴性乳腺癌4T1细胞增殖和迁移。
方法
将hUCBMSC转染miR-125a，再以优化的温和超声孵育法将DTX装载入转染和未转染外泌体。通过MTT、形态分析、划痕愈合及Transwell侵袭实验比较抗癌和抗转移效果，并以共聚焦和场发射扫描电镜观察F-actin及细胞核破坏。
结果
外泌体载药量为每微克约8.86纳克DTX，miRNA保留率约12.31%。共载制剂在4T1细胞中的IC50为192.8 ng/ml，约为游离DTX（472.8 ng/ml）的0.42倍。36小时后，共载制剂使划痕宽度增加约6.14%，而游离DTX和单独miR-125a外泌体分别仅有18.71%和77.36%的伤口闭合。共载处理还显著降低侵袭，并引起明显细胞骨架降解和细胞核变形。
意义
hUCBMSC外泌体共同装载DTX和miR-125a可产生协同促凋亡及抗迁移作用。
展开英文摘要原文
AIM: Exosomes, as a nanocarrier for the co-delivery of biologicals and small anticancer molecules is yet in its infancy.
Herein, we investigated hUCBMSC derived exosomes as a biogenic nanocarrier for the co-delivery of tumor suppressor miR-125a and microtubule destabilizing Docetaxel (DTX) to target the proliferative and migratory aggressiveness of the murine TNBC 4T1 cells. MAIN METHODS: In this study, hUCBMSCs from the human umbilical cord blood cells (hUCB) were successfully transfected with miR-125a.
Thereafter, DTX was encapsulated into both non-transfected and transfected exosomes by optimized mild sonication-incubation technique. The anticancer efficiency of hUCBMSC Exo-DTX and miR-125a Exo-DTX was compared by MTT and morphometric assay. The prominent anti-metastatic behaviour of the latter was confirmed by in-vitro wound healing and transwell invasion assay.
Further, the synergistic effect of miR-125a and DTX was confirmed by F-actin and nuclear degradation by confocal and FESEM assay. KEY FINDINGS: hUCBMSC exosomes exhibited DTX payload of 8. 86 1. 97 ng DTX/ g exosomes and miRNA retention capacity equivalent to 12. 31 5. 73 %. The co-loaded formulation (miR-125a Exo-DTX) exhibited IC 50 at 192. 8 ng/ml in 4T1 cells, which is almost 2. 36 folds' lower than the free DTX IC 50 (472. 8 ng/ml).
Additionally, miR-125a Exo-DTX treatment caused wound broadening upto 6. 14 0. 38 % while treatment with free DTX and miR-125a exosomes alone caused 18. 71 4. 5 % and 77. 36 10. 4 % of wound closure respectively in 36 h. miR-125a Exo-DTX treatment further exhibited significantly reduced invasiveness of 4T1 cells (by 3. 5 1. 8 %) along with prominent cytoskeletal degradation and nuclear deformation as compared to the miR-125a exosomes treated group.
The miR-125a expressing DTX loaded exosomal formulation clearly demonstrated the synergistic apoptotic and anti-migratory efficiency of the miR-125a Exo-DTX. SIGNIFICANCE: The synergistic anticancer and anti-metastatic effect of miR-125a Exo-DTX was observed due to presence of both DTX and miR-125a as the cargo of hUCBMSC derived exosomes.
论文信息
- 作者
- Basak M、Sahoo B、Chaudhary DK、Narisepalli S、Tiwari S、Chitkara D、Mittal A
- 第一作者单位
- Department of Pharmacy, Birla Institute of Technology and Science (BITS PILANI), Pilani, Rajasthan 333031, India.India
- 通讯作者单位
- Department of Pharmacy, Birla Institute of Technology and Science (BITS PILANI), Pilani, Rajasthan 333031, India. Electronic address: anupama.mittal@pilani.bits-pilani.ac.in.India
- 期刊
- Life sciences2023 Jun 1
- 原文标识
- PubMed 37001803 · DOI 10.1016/j.lfs.2023.121621